Mental illness is characterized by symptomatic neurological disturbances in a person's thoughts, behaviors, and/or emotions. The term is used to describe a vast array of disorders that affect people of all ages, races, cultures, and socioeconomic classes. Onset may be acute or insidious, and the symptoms may themselves be characterized as ranging from mild to severely disabling.
There is significant comorbidity of mental illness and disturbances of the gastrointestinal tract. Reports indicate that the prevalence rate of gastrointestinal illness is two to three times higher in persons with mental illness than in the normal population. The true level of comorbidity may be far greater than current studies suggest. It has been reported that psychiatric patients do not complain of gastrointestinal symptoms until specifically questioned. One prevailing belief is that the “stress” of coping with a mental illness leads to gastrointestinal disturbances. This diminishes the significance of the gastrointestinal symptoms. Moreover, many of the medications used to treat mental illness may cause gastrointestinal side effects, thus certain symptoms are may wrongly be dismissed as treatment-related.
The gastrointestinal tract is a highly complex ecosystem with as many as 300-400 bacterial species from 30 genera. Typical bacterial counts in the colon are 1011-12 per gram of feces, and the bacterial composition of multiple specimens collected over time from single individuals appears to be quite stable. Competition for available nutrients and space limits bacterial growth in the colon and contributes to the delicate, yet relatively stable, balance of organisms. This balance is disrupted by the use of broad-spectrum antimicrobials. Large numbers of the intestinal population are killed by broad-spectrum antimicrobial use, substantially diminishing the colonization resistance of the host to deleterious microbes, such as gram-positive, spore-forming anaerobic bacteria. These bacteria are often ubiquitous in nature and are readily found in numerous environments. Approximately 10% of the organisms found in a human stool specimen belong to the Clostridium genus. When growth conditions become unfavorable, the bacteria produce spores that tolerate extreme conditions that the vegetative form of the bacteria cannot survive, such as those encountered during antimicrobial treatment.
Published data along several paths may lend credence to the notion that an alteration in gastrointestinal flora contributes to symptoms of mental illness. The first line of evidence is from literature relating to infant botulism. This condition was first recognized as a distinct clinical entity in 1976. It differs from classical botulism in that the intestinal tract becomes colonized by Clostridium botulinum and elaboration of the neurotoxin occurs in vivo. Age is a primary risk factor for the development of infant botulism as diagnosis of the disease is rare after 1 year of age. However, the colonization resistance observed in mature animals is greatly diminished when they are treated with broad-spectrum antimicrobials. Similarly, antimicrobial use has been identified as a risk factor for the development of botulism related to intestinal colonization with C. botulinum in older children and adults.
The second line of evidence is from human and animal studies which have repeatedly demonstrated that intestinal colonization by opportunistic pathogens such as Escherichia coli, Klebsiella pneumoniae, Pseudomonas aerguinosa, Salmonella enteritidis, Shigella flexneri, and Vibrio cholerae. Intestinal colonization is greatly enhanced when protective intestinal microbiota are disrupted by broad-spectrum antimicrobials. In humans, the best-documented example of opportunistic colonization of the intestinal tract following antimicrobial use is that by Clostridium difficile, the causative agent of pseudomembranous colitis.
Another relevant condition is d-lactic acidosis, in which associated neurological and psychiatric symptoms are well-documented. D-lactic acidosis, a complication of short bowel syndrome or intestinal bypass surgery for obesity, is a condition caused by a change in bacterial flora to an acid-tolerant, aciduric flora. D-lactic acidosis creates a host of behavioral changes such as hostility, slurred speech, stupor, altered mental status, dizziness, asterixis, and ataxia. Treatment is with oral antimicrobials, resulting in rapid cessation of mental signs.
Certain clostridial species produce the most potent neurotoxins known to man. To date, researchers have identified seven serotypes of botulinum neurotoxin (BONT A to G) produced by at least four different clostridial species; C. botulinum, C. baratii, C. butyricum, and C. argentinense. Thus far, only C. tetani is known to produce tetanus neurotoxin (TeTX). The structural genes for clostridial neurotoxin production are chromosomal (BONT type A, B, E, and F), plasmid-associated (TeTX and BONT-G), or bacteriophage-associated (BONT type C, D, and possibly F) DNA. Plasmids and bacteriophages are natural vehicles for the transfer of genetic material between bacteria, including the genes that control neurotoxin production. It is widely accepted and believed that additional clostridial species are capable of neurotoxin production.
Research has demonstrated that tetanus neurotoxin can be transported to the central nervous system (CNS) via retrograde intra-axonal transport along the vagus nerve. Based on this finding, a clostridial neurotoxin, related to TeTX, elaborated by an organism that has colonized the intestinal tract, could gain access to the CNS via retrograde intra-axonal transport along afferent fibers of the vagus nerve. Once the toxin gained access to the CNS, cleavage of synaptic proteins would severely disrupt the delicate balance of neurotransmitters and cause behavioral symptoms indicative of mental illness, as evidenced by laboratory experiments in animals.
Behavioral symptoms have previously been associated with certain infectious diseases. Specific examples of bacteria that may cause psychological symptoms are the causative agent of syphilis, Treponema pallidum, and the causative agent of Lyme disease, Borrelia burgdrferi. The association of certain gastrointestinal illnesses with neurological and psychological symptoms is also recognized, as in d-lactic acidosis. In spite of the recognized association between bacteria and neurological and psychological symptoms in certain conditions, the possibility that the vast majority of mental illnesses symptoms are caused by a bacterial infection of the intestinal tract is a paradigm shift.